It is known that the implantation of an article or material into soft tissue initiates a sequence of physiological events in which the body attempts to remove or isolate the foreign entity. Macrophages at the site endeavor to ingest the foreign body, in some cases coalescing to form multinuculated giant cells. The presence of an implant may lead to the formation of a collagen layer of increased density as part of the host's attempt to isolate the foreign body. Such layer is commonly referred to as the "fibrous capsule" and its formation is dependent on a multiplicity of factors including surgical procedure, implant shape and size, relative movement between the implant and surrounding tissue, and surface charge and morphology.
The "classical" tissue response, as it has come to be known, is depicted somewhat schematically in FIG. 1. That figure represents a typical histological section, taken through a tissue block removed at four weeks from a dorsal implant in a Sprague-Dawley rat, of a cast silicone rubber disc 10 approximately 1 centimeter in diameter and 0.1 centimeter in thickness. It is characterized by the presence of macrophages and multinucleated giant cells 11 adjacent to the polymer surface 10a, a relatively thick fibrous capsule 12 (an average of 106 microns measured in 20 rat implants), and a layer of fat cells 13 that contain a minimal number of blood vessels and capillaries 14. In addition, the vascularity is spaced a substantial distance from the implant surface 10a.
It has been observed by investigators that the surface morphology of an implant may alter this response, as where the surface is provided with a multiplicity of projections or micropillars. In such a case, the fibrous capsule covering the micropillars has been found to be notably thinner in comparison with a fibrous capsule extending over a smooth-surface implant of the same material. Micropillars have also been found to influence the density, vascularity, and cellularity of the capsule, with such alterations being thought dependent more on the height of the pillars (at least 100 microns) than on their width. Picha, G.J., and Gibbons, D.F., "Final Report of the Effect of Controlled Surface Morphology on the Subcutaneous Tissue Response," NASA Report CR-165319, Section III, p. 2, Mar. 1981.
One aspect of this invention lies in the discovery that the width of such pillars and the distance between them, and the site of implantation in soft tissue, are also of significance in achieving an implant that yields a "non-classical" tissue response, and further, that such a response is highly significant if the implant is a mass-transfer device such as, for example, a sensor or a drug infusion device. If the width and spacing of the micropillars are both below 5000 microns, preferably below 3000 microns, and if the pillars exceed 100 microns in height, then a number of phemomena are found to occur. The thickness of the fibrous capsule is less than it would otherwise be if the surface of the implant were smooth rather than textured, with the result that the apertured or membrane-covered micropillars may protrude through the fibrous capsule into the tissue layer containing fat cells and blood vessels. Also, surprisingly, an increase in the vascularity of the tissue layer occurs. Such increased vascularity in close proximity to the ends of the pillars improves mass transfer of circulating organic substances between the vasculature and the implant.
In brief, the mass-transfer device takes the form of a supporting member or substrate having a surface textured to define a regular array of micropillars and valleys, and either a thin continuous diffusion membrane of substantially uniform thickness covering the micropillars and valleys and conforming with the surface texture of the member or, alternatively, microscopic apertures formed in the ends of the pillars through which a drug solution is slowly discharged into the surrounding tissue. Each micropillar, whether membrane covered or not, has a height no less than 100 microns and a width no greater than 5000 microns, with adjacent micropillars of the array being spaced apart a distance no greater than 5000 microns.
The micropillars may be generally rectangular (square) in section, or may be cylindrical in shape in any case preferably having a width within the range of about 25 to 3000 microns and being spaced apart a distance within the range of about 25 to 3000 microns. Where the implant takes the form of a sensor, such as a blood glucose sensor, the member or substrate may be electrically conductive and include in its composition a material capable of catalyzing a reaction with a selected blood analyte diffusible through the continuous membrane cover. Alternatively, if the implant is a drug infusion device, then the member or substrate may provide a reservoir containing an aqueous solution of the therapeutic agent and a multiplicity of passages leading from the reservoir and terminating in discharge apertures at the ends of the pillars. The drug may be discharged into the soft tissue directly through such apertures or may diffuse through a continuous membrane extending over the pillars and conforming to the contour of such pillars and the valleys between them.
Other features, advantages, and objects of the invention will become more apparent from the specification and drawings.